Here below a structured abstract about stem cells from the 22 November issue of the journal Science. The authors of this review article are: Michael H. Sieweke and Judith E. Allen.
Background
Many mature cells of the body are continuously replaced, particularly in tissues that are most exposed to the environment such as cells of the immune system. The need for new cells is driven by cellular turnover during normal tissue homeostasis and is further increased upon infection. Because differentiated cells typically withdraw from the cell cycle, replacement of mature cells is generally thought to depend on differentiation of self-renewing, tissue-specific stem cells. Until recently, tissue macrophages were thought to follow such a pathway, developing from hematopoietic stem cells via bone marrow–progenitor and blood monocyte intermediates. But this view has changed of late with several observations indicating that macrophages can self-renew by local proliferation of mature differentiated cells.
Macrophage origin and self-renewal. In the classical view, macrophages develop from self-renewing hematopoietic stem cells (HSC) in the bone marrow (BM) via blood monocyte intermediates. However, new data show that some adult tissue macrophage populations develop from embryonic progenitors independent of HSCs and can self-renew. Local proliferation can assure homeostatic maintenance (dotted arrows) and dramatically increase cell number (solid arrows) upon challenge. From https://www.sciencemag.org/content/342/6161/1242974.abstract
Advances
Recent studies have demonstrated that in macrophages, differentiation and cell cycle withdrawal can be uncoupled by the inactivation of specific transcription factors. These cells can then be expanded indefinitely as functionally differentiated macrophages without tumorigenic transformation. At the same time, it became clear that mature macrophages could also expand massively in vivo in response to infections by local proliferation, independently of input from adult hematopoietic stem cells. Furthermore, several populations of tissue macrophages were found to be derived from embryonic progenitors, and macrophages can be self-maintained in adult tissues by local proliferation. Together, these recent data suggest that macrophages are mature differentiated cells that may be endowed with self-renewal capacity akin to that of stem cells.
Outlook
These findings challenge the classical view of tissue maintenance by adult tissue-specific stem cells and indicate that stem cell–like self-renewal mechanisms may be activated in mature differentiated cells. It will be important to determine whether the engaged pathways resemble those active in stem cells and whether they might be activated in other cell types as well. Furthermore, we need to understand how such self-renewal capacity differs from uncontrolled proliferation induced by oncogenic transformation. A first step will be to explore how macrophage proliferation is regulated in vivo: How do macrophages adapt their cell numbers to diverse tissue requirements, from near quiescence during homeostasis to massive expansion under challenge? Macrophages are present in nearly every tissue and serve important functions in immunity, cancer, metabolism, and tissue repair. The role of local macrophage proliferation in these processes has remained largely unexplored. It will be important to investigate how the consequences of macrophage accumulation by local proliferation differ from those of monocyte-derived macrophage recruitment under inflammatory conditions. The control of macrophage numbers independent of inflammatory signals may provide new opportunities for therapeutic intervention in many of these areas.
Macrophage Makeover
Macrophages are important immune cells that function in tissue repair during homeostasis and in the innate immune response. Inflammation, which can be triggered by infection, is accompanied by a massive expansion of macrophages in affected tissues. The major source of this increase in resident macrophages has been thought to be hematopoietic stem cells in the bone marrow. However, recent results have shown that the mature differentiated macrophages residing in the affected tissues can themselves proliferate to boost cell numbers. Sieweke and Allen (10.1126/science.1242974) review what we know about the origin of macrophages and outline the consequences of local macrophage proliferation for the immune response and tissue homeostasis.
More information about the article: Science 22 November 2013 Vol. 342 no. 6161
Authors and affiliations:Michael H. Sieweke1 2 3 4
Judith E. Allen5
1Centre d’Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. 2Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. 3Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France. 4Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, Germany. 5Centre for Immunity, Infection and Evolution, and the Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK.
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